12-32327475-G-A

Variant names:

• chr12-32327475-G-A
• rs1163350046
• NM_001714.4:c.1020G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001714.4(BICD1):​c.1020G>A​(p.Lys340Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BICD1 NM_001714.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

BICD1 (HGNC:1049): (BICD cargo adaptor 1) This gene encodes an adaptor protein that belongs to the bicaudal D family of dynein cargo adaptors. The encoded protein acts as an intracellular cargo transport cofactor that regulates the microtubule-based loading of cargo onto the dynein motor complex. It also controls dynein motor activity and coordination. It has a domain architecture consisting of coiled-coil domains at the N- and C-termini that are highly conserved in other family members. Naturally occurring mutations in this gene are associated with short telomere length and emphysema. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.27 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	NM_001714.4	MANE Select	c.1020G>A	p.Lys340Lys	synonymous	Exon 5 of 10	NP_001705.2	Q96G01-1
	BICD1	NM_001413156.1		c.1020G>A	p.Lys340Lys	synonymous	Exon 5 of 9	NP_001400085.1
	BICD1	NM_001413157.1		c.1020G>A	p.Lys340Lys	synonymous	Exon 5 of 10	NP_001400086.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD1	ENST00000652176.1	MANE Select	c.1020G>A	p.Lys340Lys	synonymous	Exon 5 of 10	ENSP00000498700.1	Q96G01-1
	BICD1	ENST00000548411.6	TSL:1	c.1020G>A	p.Lys340Lys	synonymous	Exon 5 of 9	ENSP00000446793.1	Q96G01-4
	BICD1	ENST00000395758.3	TSL:1	n.1020G>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000379107.3	A8MVZ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448664 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718638

African (AFR) AF: 0.00 AC: 0 AN: 33096

American (AMR) AF: 0.00 AC: 0 AN: 43078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25610

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 85044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103724

Other (OTH) AF: 0.00 AC: 0 AN: 59744

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.6
DANN	Benign	0.57
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1163350046; hg19: chr12-32480409;